Effects of a cold environment or age on methamphetamine-induced dopamine release in the caudate putamen of female rats

Pharmacol Biochem Behav. 1993 Jan;44(1):87-98. doi: 10.1016/0091-3057(93)90284-z.


Extracellular levels of dopamine (DA) and metabolites as well as serotonin [5-hydroxytryptamine (5-HT)] and 5-hydroxyindoleacetic acid (5-HIAA) were determined in the caudate putamen (CPU) of either 6- or 12-month-old female rats using microdialysis and high-performance liquid chromatography with electrochemical detection (HPLC-ED) before, during, and after four consecutive injections (given at 2-h intervals) of methamphetamine (METH). In 6-month-old rats administered 4 x 5 mg/kg METH at an environmental temperature (ET) of 23 degrees C, peak extracellular DA levels (between 50 and 150 rho g/10 microliters) were attained 30-45 min after each dose of METH while dihydroxyphenylacetic acid (DOPAC) decreased steadily after the first doses of METH until it reached a plateau at 50% of control (550-700 pg/10 microliters) levels. Increases in 5-HT levels during METH administrations paralleled DA increases while 5-HIAA decreases paralleled DOPAC decreases. The total CPU DA and 5-HT content of these rats was about 65% of control at 3 days post-METH. Reducing the ET to 4 degrees C during dosing decreased the peak and average DA levels attained during the 4 x 5 mg/kg METH administration to about 50% of that observed at a 23 degrees C ET. Increasing the dose to 4 x 10 mg/kg METH (4 degrees C ET) increased peak and average CPU DA levels to 200% that observed during 4 x 5 mg/kg METH at a 23 degrees C ET. However, no significant decreases in total CPU DA content of any rats dosed with METH at a 4 degrees C ET were observed 3 days post-METH. In 12-month-old rats dosed with 4 x 5 mg/kg METH (23 degrees C ET), the peak and average extracellular DA levels were only 30-60% that of 6-month-old rats. However, the CPU DA content of older rats was significantly decreased both 3 (30% control) and 14 (60% control) days post-METH. In summary, METH toxicity may not be predicted solely by the extracellular levels of DA attained during METH administration; age and ET also greatly influence METH neurotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Aging / metabolism*
  • Animals
  • Biogenic Monoamines / metabolism
  • Caudate Nucleus / drug effects
  • Caudate Nucleus / metabolism*
  • Chromatography, High Pressure Liquid
  • Cold Temperature*
  • Dialysis
  • Dopamine / metabolism*
  • Female
  • Glutamates / metabolism
  • Glutamic Acid
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Methamphetamine / pharmacology*
  • Putamen / drug effects
  • Putamen / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / metabolism
  • Taurine / metabolism


  • Biogenic Monoamines
  • Glutamates
  • 3,4-Dihydroxyphenylacetic Acid
  • Taurine
  • Serotonin
  • Glutamic Acid
  • Methamphetamine
  • Dopamine